> Key Points

> Question - For inpatients with moderate to severe depression, is repeated intravenous ketamine superior to a psychoactive placebo (midazolam) in reducing depressive symptoms?

> Findings - In this randomized clinical trial, there was no statistically significant difference in the primary outcome, end-of-treatment Montgomery-Åsberg Depression Rating Scale score, between the ketamine and midazolam groups. No significant differences were observed on secondary efficacy, cognitive, economic, or quality-of-life outcomes.

> Meaning - These findings do not support a superior antidepressant effect for serial intravenous ketamine infusions as an adjunctive therapy to usual inpatient care for moderate to severe depression.